Discovery, translation, and clinical implementation of molecular markers for cancer diagnosis and treatment.

Research Description: Dr. Bepler's research efforts have been focused on the discovery, translation, and clinical implementation of molecular markers for therapeutic decisions in patients with malignancies. In particular, the focus has been on molecules that are involved in efficacy of antimetabolites, such as gemcitabine and pemetrexed, and DNA damaging agents, such as platinum compounds, in lung cancer. Initially, his lab discovered that the regulatory subunit of ribonucleotide reductase (RRM1) was located in a region of frequent allele loss in lung cancer. He was among the first to demonstrate that RRM1 was involved cell proliferation, migration, and invasion and was protective of carcinogen-induced lung tumor formation. His lab was also among the first to demonstrate that RRM1 is the major determinant of gemcitabine efficacy. He conducted the first trial in patient with lung cancer where chemotherapeutic agents were selected based on tumoral levels of RRM1 and ERCC1 expression. These discoveries and approaches are now being applied to other malignancies including but not limited to pancreatic cancer and urothelial malignancies.